First ever CD4 cell count after primary infection can predict immune restoration during HIV therapy

The level of a patient’s CD4 cell count shortly after infection with HIV can predict the extent of immune recovery after the initiation of antiretroviral therapy, investigators from the US military report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“The baseline CD4⁺ T cell count observed during the early stages of HIV infection is a strong predictor of CD4⁺ T cell count attained after HAART [highly active antiretroviral therapy],” comment the authors.

They believe that their findings have implications for HIV care, especially the current debate about the best time to initiate therapy with antiretroviral drugs: “Our results indicate that it may be clinically useful to consider the baseline CD4⁺ T cell count as an approximate guideline for targeting the post-HAART recovery.”

CD4 cell count is used as a guide to help doctors and patients decide when to start HIV therapy. Current US guidelines recommend that an individual should start treatment when their CD4 cell count is around 500 cells/mm³.

Initiation of therapy at higher CD4 cell counts has been shown to reduce the risk of both HIV-related and non-HIV-related illnesses. Moreover, the timing of therapy can also have an impact on immune recovery. Patients who wait to start HIV treatment until their CD4 cell count is in the region of 200 cells/mm³ are less likely to achieve the same levels of immune restoration as patients with initiate therapy at higher CD4 cell counts.

However, the relationship between CD4 cell count in the period shortly after infection with HIV (baseline) and subsequent improvements in immune function after the commencements of antiretroviral treatment is unknown.

Therefore researchers from the US military’s HIV Natural History Study undertook a longitudinal study to assess the impact of immune function soon after HIV seroconversion, as well as the lowest ever, or nadir, CD4 cell count on immune restoration two years after the initiation of HIV therapy.

A total of 1084 HIV-positive US military personnel who received care between 1996 and 2008 were included in the study. These individuals were regularly tested for HIV, and the median period between a negative and positive HIV antibody test was 1.37 years.

At the time of their diagnosis the patients had a median CD4 cell count of 470 cells/mm³.

Median nadir CD4 cell count was 311 cells/mm³. All the patients started antiretroviral therapy and 93% achieved virological control.  Two years after starting HIV therapy the patients’ median CD4 cell count had increased to 577 cells/mm³.  

A strong relationship was found between a lower baseline CD4 cell count and poorer immune recovery during HIV therapy.

Patients with a first ever CD4 cell count below 500 cells/mm³ were over three times more likely than individuals with higher baseline CD4 cell counts to have an average CD4 cell count below 500 cells/mm³ over two years after starting HIV therapy (odds ratio [OR] = 3.19; 95% CI, 2.27-4.49).

Further analysis showed that the relationship between CD4 cell count soon after infection with HIV and CD4 cell count after two years of treatment was largely independent of nadir CD4 cell count, and that baseline CD4 cell count accounted for between 50-74% of subsequent immune recovery.

Nevertheless, nadir CD4 cell count was important. During HIV therapy the highest CD4 cell counts were seen in patients who had a baseline CD4 cell count above 700 cells/mm³ and a nadir CD4 cell count of at least 200 cells/mm³.

In multivariate analysis a significant relationship was identified between a higher first ever CD4 cell count and CD4 cell gain during treatment (p < 0.001).   However, a lower nadir CD4 cell count was associated with poorer improvements in immune function (p < 0.001).

However, the investigators observed that for “a given nadir CD4 count, a higher baseline CD4⁺ T cell count was associated with a larger gain after HAART.”

There was also a relationship between the extent of CD4 cell decline prior to the initiation of therapy and subsequent recovery during HIV treatment.

Patients whose nadir CD4 cell count was at least 60% of the baseline value when they started HIV therapy were significantly more likely to experience reconstitution of their CD4 cell count to that recorded soon after infection.

“We developed a novel marker, the nadir/baseline ratio as one with a high degree of association with future course of immune reconstitution after HAART,” write the authors.

“This finding further implies that a) it may be useful to have a knowledge of baseline CD4⁺ T cell count as close to seroconversion as feasible; and b) if the CD4⁺ T cell count falls below 60% of this value, the situation is less likely to yield a robust immune reconstitution even if viral load suppression is achieved.”

The investigators add that their findings are “in line with the view that early HIV-diagnosis and HAART initiation can be beneficial. Second, our study implies that knowledge of the baseline CD4⁺ T cell count may provide a clinician with a realistic therapeutic goal for CD4 recovery following HAART.”